Macroaggregates of copper-64 and gelatin,application and method of preparation of same

ABSTRACT

IN A METHOD OF PREPARATION OF MACROAGGREGATES OF COPPER-64 AND GELATIN FOR USE IN RADIOACTIVE TRACER STUDIES, MEDICAL DIAGNOSTIC TESTS AND SCANNING TECHNIQUES, AN ALKALINE SOLUTION OF COPPER-64 IS ADDED IN THE COLD STATE TO A SOLUTION OF GELATIN SO AS TO FORM A COPPER-GELATIN COMPLEX. THIS COMPLEX IS PRECIPITATED IN THE HOT STATE BY A SOLUTION OF TANNIN AND THE SUSPENSION OBTAINED IS THEN COMPLETED BY ADDITION OF DISTILLED WATER. THE PROPORTIONS ARE CALCULATED SO AS TO MAINTAN A PH IN THE VICINTIY OF 7 OR IN OTHER WORDS A NEUTRAL VALUE AND IN SUCH A MANNER AS TO ENSURE THAT THE SUSPENSION DOES NOT CONTAIN COPPER IN THE IONIC FORM OF ANY GELATIN WHICH HAS REMAINED IN SOLUTION.

United States Patent MACROAGGREGATES 0F COPPER-64 AND GELA- TIN, APPLICATION AND METHOD OF PREPA- RATION OF SAME Christian Gelis, Montpellier, France, assignor to Commissariat a IEnergie Atomique, Paris, France No Drawing. Filed May 18, 1970, Ser. No. 38,489 Claims priority, applic6a9tio7r5 lgrance, May 28, 1969,

Int. Cl. A61k 27/04; Gfllt 1/00 US. Cl. 4241 Claims ABSTRACT OF THE DISCLOSURE in a method of preparation of macroaggregates of copper-64 and gelatin for use in radioactive tracer studies, medical diagnostic tests and scanning techniques, an alkaline solution of copper-64 is added in the cold state to a solution of gelatin so as to form a copper-gelatin complex. This complex is precipitated in the hot state by a solution of tannin and the suspension obtained is then completed by addition of distilled water. The proportions are calculated so as to maintain a pH in the vicinity of 7 or in other words a neutral value and in such a manner as to ensure that the suspension does not contain copper in the ionic form of any gelatin which has remained in solution.

The present invention relates to macroaggregates of copper-64 and gelatin as well as to a method of preparation of macroaggregates of thin type and to their uses in human medicine, one application for which these macroaggregates are of particular interest being in the field of pulmonary scintiscanning by intravenous injection.

A radioactive preparation which is intended to be employed in pulmonary scintiscanning must exhibit properties which permit retention of said preparation at the level of the pulmonary alveoli without causing any permanent obstruction of the capillary system. This entails the need to ensure that the particles of a preparation of this type must be of sufficiently large size in order to be efiFective while remaining sufficiently small and friable to ensure that the aggregate which is formed by said particles can readily be broken down by the blood stream.

A particle diameter of the order of 50 microns makes it possible to satisfy these two conditions.

Moreover, in pulmonary scintiscanning, considerable importance must be attached to the radiation and to the half-life of the radioactive element which is employed and which must permit detection by external measurement without delivering a radiation dose of unnecessarily high value.

As is well known, it is a common practice in pulmonary scintiscanning to make use of human serum albumin labelled with iodine-131. However, the present applicant has found that the use of copper'64 (radioactive copper) was preferable on the one hand by reason of the fact that copper-64 emits in particular fl-i-radiations and that its half-life (12.8 hours) is shorter than that of radioactive iodine and on the other hand by reason of the fact that the association of copper-64 and gelatin makes it possible to obtain particles having a diameter which satisfies the conditions stated in the foregoing.

In more exact terms, this invention relates to the novel industrial product which is constituted by the macroaggregates of copper-64 and gelatin.

The invention is also concerned with a method of preparation of macroaggregates of copper-64 and gelatin which essentially consists in forming a copper-gelatin compleX by addition in the cold state of an alkaline solution of copper-64 to a solution of gelatin, in precipitating said complex in the hot state with a solution of tannin 'ice and in completing the suspension obtained by addition of distilled water, the proportions being calculated so as to maintain a pH in the vicinity of 7 or in other words a neutral value and in such a manner as to ensure that said suspension does not contain any copper in the ionic form or any gelatin which has remained in solution.

The present invention is further concerned with the applications of the macroaggregates of copper-64 and gelatin in the field of human medicine.

Further properties and advantages of this invention will be brought out in the description which now follows and in which one form of execution of the method according to the invention is given by way of explanation but without limitation.

The stages of this method or process are as follows:

(a) Preparation of a solution of gelatin 10 g. of gelatin are dispersed in cm. of distilled water at 80 C. for a period of two hours. The solution which is obtained is then sterilized in an autoclave at C. for a period of 20 minutes.

(b) Preparation of an alkaline solution of copper 50 mg. of copper-64 are treated in the hot state with 6 N hydrochloric acid in the presence of nitric acid.

The copper chloride obtained is washed a number of times, then crystallized and retreated with a small quantity of water. There are then added 3.8 cm. of an 8% solution of double tartrate of sodium and potassium, then 1 cm. of a 2 N sodium hydroxide solution and finally the quantity of distilled water which is necessary to produce a volume of 7.8 cm, which corresponds to a concentration of 6.4 mg. of copper-64 per liter.

(c) Formation of a copper-64/ gelatin complex 0.5 cm. of the alkaline solution of copper obtained in stage (b) is contacted with 0.5 cm. of the gelatin solution obtained in stage (a). A purplish-blue complex is thus obtained.

(d) Formation of the macroaggregates The complex obtained in stage (c) is precipitated and heated to a temperature of 50 C. by addition of 0.25 cm. of a 12% solution of tannin and the suspension is completed to 10 cm. by addition of distilled water.

It is evident that the example which has been set forth above has been given solely by way of indication but that the proportions must in any case be such that the pH should be maintained in the vicinity of the neutral value, that there should not remain any copper-64 in excess (which would necessarily be in the ionic form) and similarly that no gelatin should be permitted to remain in excess since this latter would be in solution and would constitute a trap for the copper-64.

The proportions given above satisfy these ditferent conditions and result in the production of macroaggregates which are suitable for use in pulmonary scintiscanning. The diameter of the particles thus obtained is suitably of the order of 50 microns and must in any case always be greater than 30 microns; this diameter varies slightly as a function of the proportion of gelatin and of tannin.

The macroaggregates obtained with the proportions given in the example and applied by means of intravenous injections to animals used for test purposes at a dose of 0.5 cm. per kilogram of animal have yielded satisfactory results in rats and rabbits (scintigraphic images of very good quality).

It is readily apparent that, in the field of human medicine, the macroaggregates in accordance with the present invention can find applications other than pulmonary scintiscanning (e.g. scintiscanning of the liver) and that a given particle diameter corresponds to each particular application.

' 3 What I claim is:

each particle having a diameter greater than 30 microns and on the order of 50 microns.

2. A method of pulmonary scintiscanning in humans consisting of the step of injecting intravenously the complex of claim 1 into the patient. 7

3. A method of preparing a copper-64/gelatin complex, each particle having a diameter greater than 30 microns and on the order of 50 microns, consisting of the steps of mixing an alkaline solution of a copper-64 salt and a solution of gelatin in the cold state, heating the mixture, precipitating a copper-64/gelatin complex by the addition of a solution of tannin, and completing the precipitation by the addition of distilled water, the proportions of the ingredients used leaving substantially no copper-64 or gelatin in solution in uncomplexed form.

4. -A method according to claim 3, the alkaline solu- 7 tion of the copper-64 salt being prepared by treating copper-64 chloride with aqueous sodium hydroxide in the presence of sodium potassium tartrate.

5. A method according to claim 3, the gelatin solution being prepared by a dispersing gelatin in hot distilled water and sterilizing the resulting solution in an autoclave.

References Cited UNITED STATES PATENTS 3,121,041 2/1964 Stern et al. 4241 3,127,313 3/1964 Glenn 4241 3,428,731 2/ 1969 'Furness 424141 BENJAMIN R. PADGETI, Primary Examiner US. Cl. X.R.'

250106 T, 71.5 S; 252-301.1 R; 424-441 

